What is a Dosage Form?

Introduction

Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a capsule shell, for example), and apportioned into a particular dose. For example, two products may both be amoxicillin, but one is in 500 mg capsules and another is in 250 mg chewable tablets.

The term unit dose can also sometimes encompass non-reusable packaging as well (especially when each drug product is individually packaged), although the US Food and Drug Administration (FDA) distinguishes that by unit-dose “packaging” or “dispensing”. Depending on the context, multi(ple) unit dose can refer to distinct drug products packaged together, or to a single drug product containing multiple drugs and/or doses. The term dosage form can also sometimes refer only to the pharmaceutical formulation of a drug product’s constituent drug substance(s) and any blends involved, without considering matters beyond that (like how it is ultimately configured as a consumable product such as a capsule, patch, etc.). Because of the somewhat vague boundaries and unclear overlap of these terms and certain variants and qualifiers within the pharmaceutical industry, caution is often advisable when conversing with someone who may be unfamiliar with another person’s use of the term.

Depending on the method/route of administration, dosage forms come in several types. These include many kinds of liquid, solid, and semisolid dosage forms. Common dosage forms include pill, tablet, or capsule, drink or syrup, among many others. In naturopathy, dosages can take the form of decoctions and herbal teas, as well as the more conventional methods previously mentioned. A liquid dosage form is the liquid form of a dose of a chemical compound used as a drug or medication intended for administration or consumption.

The route of administration (ROA) for drug delivery is dependent on the dosage form of the substance in question. Various dosage forms may exist for a single particular drug, since some medical conditions such as being unconscious can restrict ROA. For example, persistent nausea, especially with vomiting, may make it difficult to use an oral dosage form, and in such a case, it may be necessary to use an alternative route such as inhalational, buccal, sublingual, nasal, suppository or parenteral instead. Additionally, a specific dosage form may be a requirement for certain kinds of drugs, as there may be issues with various factors like chemical stability or pharmacokinetics. As an example, insulin cannot be given orally because upon being administered in this manner, it is extensively metabolized in the gastrointestinal tract (GIT) before reaching the blood stream, and is thereby incapable of sufficiently reaching its therapeutic target destinations. The oral and intravenous doses of a drug such as paracetamol will differ for the same reason.

Oral

  • Pills, i.e. tablets or capsules.
  • Liquids such as syrups, solutions, elixers, emulsions, and tinctures.
  • Liquids such as decoctions and herbal teas.
  • Orally disintegrating tablets.
  • Lozenges or candy (electuaries).
  • Thin films (e.g. Listerine Pocketpaks, nitroglycerin) to be placed on top of or underneath the tongue as well as against the cheek.
  • Powders or effervescent powder or tablets, often instructed to be mixed into a food item.
  • Plants or seeds prepared in various ways such as a cannabis edible.
  • Pastes such as high fluoride toothpastes.
  • Gases such as oxygen (can also be delivered through the nose).

Ophthalmic

  • Eye drops.
  • Lotions.
  • Ointments.
  • Emulsions.

Inhalation

  • Aerosolised medication.
  • Dry-powder Inhalers or metered dose inhalers.
  • Nebuliser-administered medication.
  • Smoking.
  • Vaporiser-administered medication.

Unintended Ingredients

Talc is an excipient often used in pharmaceutical tablets that may end up being crushed to a powder against medical advice or for recreational use. Also, illicit drugs that occur as white powder in their pure form are often cut with cheap talc. Natural talc is cheap but contains asbestos while asbestos-free talc is more expensive. Inhaled talc that has asbestos is generally accepted as being able to cause lung cancer if it is inhaled. The evidence about asbestos-free talc is less clear, according to the American Cancer Society.

Injection

  • Parenteral.
  • Intradermally-administered (ID).
  • Subcutaneously-administered (SC).
  • Intramuscularly-administered (IM).
  • Intraosseous administration (IO).
  • Intraperitoneally-administered (IP).
  • intravenously-administered (IV).
  • Intracavernously-administered (ICI).

These are usually solutions and suspensions.

Unintended Ingredients

Safe

Eye drops (normal saline in disposable packages) are distributed to syringe users by needle exchange programs.

Unsafe

The injection of talc from crushed pills has been associated with pulmonary talcosis in intravenous drug users.

Topical

  • Creams, liniments, balms (such as lip balm or antiperspirants and deodorants), lotions, or ointments, etc.
  • Gels and hydrogels.
  • Ear drops.
  • Transdermal and dermal patches to be applied to the skin.
  • Powders.

Unintended Use

  • It is not safe to calculate divided doses by cutting and weighing medical skin patches, because there’s no guarantee that the substance is evenly distributed on the patch surface. For example, fentanyl transdermal patches are designed to slowly release the substance over 3 days. It is well known that cut fentanyl transdermal consumed orally have cause overdoses and deaths.
  • Single blotting papers for illicit drugs injected from solvents in syringes may also cause uneven distribution across the surface.

Other

  • Intravaginal administration:
    • Vaginal rings.
    • Capsules and tablets.
    • Suppositories.
  • Rectal administration (enteral):
    • Suppositories.
    • Suspensions and solutions in the form of enemas.
    • Gels.
  • Urethral.
  • Nasal sprays.

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What is Hallucinogen Persisting Perception Disorder?

Introduction

Hallucinogen persisting perception disorder (HPPD) is a chronic and non-psychotic disorder in which a person experiences apparent lasting or persistent visual hallucinations or perceptual distortions after a previous hallucinogenic drug experience, usually lacking the same feelings of intoxication or mental alteration experienced while on the drug.

The hallucinations and perceptual changes themselves are usually not intense or impairing and consist of visual snow, trails and after images (palinopsia), light fractals on flat surfaces, intensified colours or other psychedelic visuals. People who have never previously taken drugs have also reported some visual anomalies associated with HPPD (such as floaters and visual snow).

To be diagnosed, the disorder must cause distress or impairment in work or everyday life. Symptoms often get worse when focused on.

Brief History

In 1898, the English writer and intellectual Havelock Ellis reported a heightened sensitivity to “the more delicate phenomena of light and shade and colour” for a prolonged period of time after consuming the psychedelic drug mescaline. This may have been one of the first recorded cases of what would later be called “HPPD”. However, mild residual effects or “afterglows” from these types of drugs are not necessarily unusual nor indicative of what can be classified as a disorder like HPPD since distress to the individual is usually a requirement for diagnosis.

HPPD Subtypes

According to a 2016 review, there are two theorized subtypes of the condition. Type 1 HPPD is where people experience random, brief flashbacks. Type 2 HPPD entails experiencing persistent changes to vision, which may vary in intensity. This model has faced scrutiny however due to “flashbacks” often being considered a separate affliction and not always a perceptual one.

Cause

HPPD is not related to psychosis due to the fact those affected by the disorder can easily distinguish their visual disturbances from reality. The only certain cause of HPPD is prior use of hallucinogens. Some evidence points to phenethylamines carrying a slightly greater risk than lysergamides or tryptamines. There are no known risk factors, and what might trigger any specific disturbing hallucination is not known. Some sort of disinhibition of visual processing may be involved. It has been suggested MDMA (ecstasy) use with other drugs is linked to the development of HPPD.

Diagnosis

HPPD is a DSM-5 diagnosis with diagnostic code 292.89 (F16.983). For the diagnosis to be made, other psychological, psychiatric, or neurological conditions must be ruled out and it must cause distress in everyday life.

Treatment

As of September 2021 there is still no good evidence of any specific medicinal treatment as being commonly effective for HPPD.

Avoiding any additional use of psychoactive drugs (including cannabis and alcohol) from an early stage of the disorder seems to be an effective way for many sufferers to achieve recovery, as these substances apparently worsen the condition over time.

Some prescription drugs (lamotrigine, clonazepam, levetiracetam and others) have been known to relieve symptoms for some, but worsen symptoms or create dependencies for others.

Antipsychotic drugs and SSRIs have also been reported to help some people temporarily but worsen symptoms for others.

Some sufferers have reported benefits from prolonged water fasting, medications like acetylcysteine and lithium, and from supplements like tyrosine, ashwagandha and lion’s mane, although some users report lion’s mane and ashwagandha as having potentially negative effects or creating dependencies.

Sunglasses and talk therapy might also help those who are dealing with HPPD, but in general it seems that maintaining sobriety from all psychoactive substances is still the best solution available for this condition.

Prevalence

The prevalence of HPPD was unknown as of 2021. Estimates in the 1960s and 1970s were around 1 in 20 for intermittent HPPD among regular users of hallucinogens. In a 2010 study of psychedelic users, 23.9% reported constant HPPD-like effects, however only 4.2% considered seeking treatment due to the severity. It is not clear how common chronic HPPD may be, but one estimate in the 1990s was that 1 in 50,000 regular users might have chronic hallucinations.

Society and Culture

In the second episode of the first season of the 2014 series True Detective (“Seeing Things”), primary character Rustin Cohle (Matthew McConaughey) is depicted as having symptoms similar to HPPD such as light tracers as a result of “neurological damage” from substance use.

American journalist Andrew Callaghan, former host of the internet series All Gas No Brakes, revealed during a 2021 interview with Vice News that he has a HPPD diagnosis as a result of excessive psilocybin use at a young age. Describing his symptoms, he noted that he experiences persistent visual snow and palinopsia.

What is Hallucination?

Introduction

A hallucination is a perception in the absence of external stimulus that has qualities of real perceptions.

Hallucinations are vivid, substantial, and are perceived to be located in external objective space. They are distinguishable from several related phenomena, such as dreaming, which does not involve wakefulness; pseudohallucination, which does not mimic real perception, and is accurately perceived as unreal; illusion, which involves distorted or misinterpreted real perception; and imagery (imagination), which does not mimic real perception, and is under voluntary control. Hallucinations also differ from “delusional perceptions”, in which a correctly sensed and interpreted stimulus (i.e. a real perception) is given some additional (and typically absurd) significance.

Hallucinations can occur in any sensory modality – visual, auditory, olfactory, gustatory, tactile, proprioceptive, equilibrioceptive, nociceptive, thermoceptive and chronoceptive.

A mild form of hallucination is known as a disturbance, and can occur in most of the senses above. These may be things like seeing movement in peripheral vision, or hearing faint noises or voices. Auditory hallucinations are very common in schizophrenia. They may be benevolent (telling the subject good things about themselves) or malicious, cursing the subject, etc. 55% of auditory hallucinations are malicious in content, for example, people talking about the subject behind their back, etc. Like auditory hallucinations, the source of the visual counterpart can also be behind the subject’s back. This can produce a feeling of being looked or stared at, usually with malicious intent. Frequently, auditory hallucinations and their visual counterpart are experienced by the subject together.

Hypnagogic hallucinations and hypnopompic hallucinations are considered normal phenomena. Hypnagogic hallucinations can occur as one is falling asleep and hypnopompic hallucinations occur when one is waking up. Hallucinations can be associated with drug use (particularly deliriants), sleep deprivation, psychosis, neurological disorders, and delirium tremens.

The word “hallucination” itself was introduced into the English language by the 17th-century physician Sir Thomas Browne in 1646 from the derivation of the Latin word alucinari meaning to wander in the mind. For Browne, hallucination means a sort of vision that is “depraved and receive[s] its objects erroneously”.

Classification

Hallucinations may be manifested in a variety of forms. Various forms of hallucinations affect different senses, sometimes occurring simultaneously, creating multiple sensory hallucinations for those experiencing them.

Visual

A visual hallucination is “the perception of an external visual stimulus where none exists”. A separate but related phenomenon is a visual illusion, which is a distortion of a real external stimulus. Visual hallucinations are classified as simple or complex:

  • Simple visual hallucinations (SVH) are also referred to as non-formed visual hallucinations and elementary visual hallucinations.
    • These terms refer to lights, colours, geometric shapes, and indiscrete objects.
    • These can be further subdivided into phosphenes which are SVH without structure, and photopsias which are SVH with geometric structures.
  • Complex visual hallucinations (CVH) are also referred to as formed visual hallucinations.
    • CVHs are clear, lifelike images or scenes such as people, animals, objects, places, etc.

For example, one may report hallucinating a giraffe. A simple visual hallucination is an amorphous figure that may have a similar shape or colour to a giraffe (looks like a giraffe), while a complex visual hallucination is a discrete, lifelike image that is, unmistakably, a giraffe.

Auditory

Auditory hallucinations (also known as paracusia) are the perception of sound without outside stimulus. These hallucinations are the most common type of hallucination. Auditory hallucinations can be divided into two categories: elementary and complex. Elementary hallucinations are the perception of sounds such as hissing, whistling, an extended tone, and more. In many cases, tinnitus is an elementary auditory hallucination. However, some people who experience certain types of tinnitus, especially pulsatile tinnitus, are actually hearing the blood rushing through vessels near the ear. Because the auditory stimulus is present in this situation, it does not qualify it as a hallucination.

Complex hallucinations are those of voices, music, or other sounds that may or may not be clear, may or may not be familiar, and may be friendly, aggressive, or among other possibilities. A hallucination of a single individual person of one or more talking voices is particularly associated with psychotic disorders such as schizophrenia, and hold special significance in diagnosing these conditions.

Another typical disorder where auditory hallucinations are very common is dissociative identity disorder. In schizophrenia voices are normally perceived coming from outside the person but in dissociative disorders they are perceived as originating from within the person, commenting in their head instead of behind their back. Differential diagnosis between schizophrenia and dissociative disorders is challenging due to many overlapping symptoms, especially Schneiderian first rank symptoms such as hallucinations. However, many people not suffering from diagnosable mental illness may sometimes hear voices as well. One important example to consider when forming a differential diagnosis for a patient with paracusia is lateral temporal lobe epilepsy. Despite the tendency to associate hearing voices, or otherwise hallucinating, and psychosis with schizophrenia or other psychiatric illnesses, it is crucial to take into consideration that, even if a person does exhibit psychotic features, he/she does not necessarily suffer from a psychiatric disorder on its own. Disorders such as Wilson’s disease, various endocrine diseases, numerous metabolic disturbances, multiple sclerosis, systemic lupus erythematosus, porphyria, sarcoidosis, and many others can present with psychosis.

Musical hallucinations are also relatively common in terms of complex auditory hallucinations and may be the result of a wide range of causes ranging from hearing-loss (such as in musical ear syndrome, the auditory version of Charles Bonnet syndrome), lateral temporal lobe epilepsy, arteriovenous malformation, stroke, lesion, abscess, or tumour.

The Hearing Voices Movement is a support and advocacy group for people who hallucinate voices, but do not otherwise show signs of mental illness or impairment.

High caffeine consumption has been linked to an increase in likelihood of one experiencing auditory hallucinations. A study conducted by the La Trobe University School of Psychological Sciences revealed that as few as five cups of coffee a day (approximately 500 mg of caffeine) could trigger the phenomenon.

Command

Command hallucinations are hallucinations in the form of commands; they can be auditory or inside of the person’s mind or consciousness. The contents of the hallucinations can range from the innocuous to commands to cause harm to the self or others. Command hallucinations are often associated with schizophrenia. People experiencing command hallucinations may or may not comply with the hallucinated commands, depending on the circumstances. Compliance is more common for non-violent commands.

Command hallucinations are sometimes used to defend a crime that has been committed, often homicides. In essence, it is a voice that one hears and it tells the listener what to do. Sometimes the commands are quite benign directives such as “Stand up” or “Shut the door.” Whether it is a command for something simple or something that is a threat, it is still considered a “command hallucination.” Some helpful questions that can assist one in figuring out if they may be suffering from this includes: “What are the voices telling you to do?”, “When did your voices first start telling you to do things?”, “Do you recognize the person who is telling you to harm yourself (or others)?”, “Do you think you can resist doing what the voices are telling you to do?”

Olfactory

Phantosmia (olfactory hallucinations), smelling an odour that is not actually there, and parosmia (olfactory illusions), inhaling a real odour but perceiving it as different scent than remembered, are distortions to the sense of smell (olfactory system), and in most cases, are not caused by anything serious and will usually go away on their own in time. It can result from a range of conditions such as nasal infections, nasal polyps, dental problems, migraines, head injuries, seizures, strokes, or brain tumours. Environmental exposures can sometimes cause it as well, such as smoking, exposure to certain types of chemicals (e.g. insecticides or solvents), or radiation treatment for head or neck cancer. It can also be a symptom of certain mental disorders such as depression, bipolar disorder, intoxication or withdrawal from drugs and alcohol, or psychotic disorders (e.g. schizophrenia). The perceived odours are usually unpleasant and commonly described as smelling burned, foul spoiled, or rotten.

Tactile

Tactile hallucinations are the illusion of tactile sensory input, simulating various types of pressure to the skin or other organs. One subtype of tactile hallucination, formication, is the sensation of insects crawling underneath the skin and is frequently associated with prolonged cocaine use. However, formication may also be the result of normal hormonal changes such as menopause, or disorders such as peripheral neuropathy, high fevers, Lyme disease, skin cancer, and more.

Gustatory

This type of hallucination is the perception of taste without a stimulus. These hallucinations, which are typically strange or unpleasant, are relatively common among individuals who have certain types of focal epilepsy, especially temporal lobe epilepsy. The regions of the brain responsible for gustatory hallucination in this case are the insula and the superior bank of the sylvian fissure.

General Somatic Sensations

General somatic sensations of a hallucinatory nature are experienced when an individual feels that their body is being mutilated, i.e. twisted, torn, or disembowelled. Other reported cases are invasion by animals in the person’s internal organs, such as snakes in the stomach or frogs in the rectum. The general feeling that one’s flesh is decomposing is also classified under this type of hallucination.

Cause

Hallucinations can be caused by a number of factors.

Hypnagogic Hallucination

These hallucinations occur just before falling asleep and affect a high proportion of the population: in one survey 37% of the respondents experienced them twice a week. The hallucinations can last from seconds to minutes; all the while, the subject usually remains aware of the true nature of the images. These may be associated with narcolepsy. Hypnagogic hallucinations are sometimes associated with brainstem abnormalities, but this is rare.

Peduncular Hallucinosis

Peduncular means pertaining to the peduncle, which is a neural tract running to and from the pons on the brain stem. These hallucinations usually occur in the evenings, but not during drowsiness, as in the case of hypnagogic hallucination. The subject is usually fully conscious and then can interact with the hallucinatory characters for extended periods of time. As in the case of hypnagogic hallucinations, insight into the nature of the images remains intact. The false images can occur in any part of the visual field, and are rarely polymodal.

Delirium Tremens

One of the more enigmatic forms of visual hallucination is the highly variable, possibly polymodal delirium tremens. Individuals suffering from delirium tremens may be agitated and confused, especially in the later stages of this disease. Insight is gradually reduced with the progression of this disorder. Sleep is disturbed and occurs for a shorter period of time, with rapid eye movement sleep.

Parkinson’s Disease and Lewy Body Dementia

Parkinson’s disease is linked with Lewy body dementia for their similar hallucinatory symptoms. The symptoms strike during the evening in any part of the visual field, and are rarely polymodal. The segue into hallucination may begin with illusions where sensory perception is greatly distorted, but no novel sensory information is present. These typically last for several minutes, during which time the subject may be either conscious and normal or drowsy/inaccessible. Insight into these hallucinations is usually preserved and REM sleep is usually reduced. Parkinson’s disease is usually associated with a degraded substantia nigra pars compacta, but recent evidence suggests that PD affects a number of sites in the brain. Some places of noted degradation include the median raphe nuclei, the noradrenergic parts of the locus coeruleus, and the cholinergic neurons in the parabrachial area and pedunculopontine nuclei of the tegmentum.

Migraine Coma

This type of hallucination is usually experienced during the recovery from a comatose state. The migraine coma can last for up to two days, and a state of depression is sometimes comorbid. The hallucinations occur during states of full consciousness, and insight into the hallucinatory nature of the images is preserved. It has been noted that ataxic lesions accompany the migraine coma.

Charles Bonnet Syndrome

Charles Bonnet syndrome is the name given to visual hallucinations experienced by a partially or severely sight impaired person. The hallucinations can occur at any time and can distress people of any age, as they may not initially be aware that they are hallucinating. They may fear for their own mental health initially, which may delay them sharing with carers until they start to understand it themselves. The hallucinations can frighten and disconcert as to what is real and what is not. The hallucinations can sometimes be dispersed by eye movements, or by reasoned logic such as, “I can see fire but there is no smoke and there is no heat from it” or perhaps, “We have an infestation of rats but they have pink ribbons with a bell tied on their necks.” Over elapsed months and years, the manifestation of the hallucinations may change, becoming more or less frequent with changes in ability to see. The length of time that the sight impaired person can suffer from these hallucinations varies according to the underlying speed of eye deterioration. A differential diagnosis are ophthalmopathic hallucinations.

Focal Epilepsy

Visual hallucinations due to focal seizures differ depending on the region of the brain where the seizure occurs. For example, visual hallucinations during occipital lobe seizures are typically visions of brightly coloured, geometric shapes that may move across the visual field, multiply, or form concentric rings and generally persist from a few seconds to a few minutes. They are usually unilateral and localised to one part of the visual field on the contralateral side of the seizure focus, typically the temporal field. However, unilateral visions moving horizontally across the visual field begin on the contralateral side and move toward the ipsilateral side.

Temporal lobe seizures, on the other hand, can produce complex visual hallucinations of people, scenes, animals, and more as well as distortions of visual perception. Complex hallucinations may appear to be real or unreal, may or may not be distorted with respect to size, and may seem disturbing or affable, among other variables. One rare but notable type of hallucination is heautoscopy, a hallucination of a mirror image of one’s self. These “other selves” may be perfectly still or performing complex tasks, may be an image of a younger self or the present self, and tend to be briefly present. Complex hallucinations are a relatively uncommon finding in temporal lobe epilepsy patients. Rarely, they may occur during occipital focal seizures or in parietal lobe seizures.

Distortions in visual perception during a temporal lobe seizure may include size distortion (micropsia or macropsia), distorted perception of movement (where moving objects may appear to be moving very slowly or to be perfectly still), a sense that surfaces such as ceilings and even entire horizons are moving farther away in a fashion similar to the dolly zoom effect, and other illusions. Even when consciousness is impaired, insight into the hallucination or illusion is typically preserved.

Drug-Induced Hallucination

Drug-induced hallucinations are caused by hallucinogens, dissociatives, and deliriants, including many drugs with anticholinergic actions and certain stimulants, which are known to cause visual and auditory hallucinations. Some psychedelics such as lysergic acid diethylamide (LSD) and psilocybin can cause hallucinations that range in the spectrum of mild to intense.

Hallucinations, pseudohallucinations, or intensification of pareidolia, particularly auditory, are known side effects of opioids to different degrees – it may be associated with the absolute degree of agonism or antagonism of especially the kappa opioid receptor, sigma receptors, delta opioid receptor and the NMDA receptors or the overall receptor activation profile as synthetic opioids like those of the pentazocine, levorphanol, fentanyl, pethidine, methadone and some other families are more associated with this side effect than natural opioids like morphine and codeine and semi-synthetics like hydromorphone, amongst which there also appears to be a stronger correlation with the relative analgesic strength. Three opioids, Cyclazocine (a benzormorphan opioid/pentazocine relative) and two levorphanol-related morphinan opioids, Cyclorphan and Dextrorphan are classified as hallucinogens, and Dextromethorphan as a dissociative. These drugs also can induce sleep (relating to hypnagogic hallucinations) and especially the pethidines have atropine-like anticholinergic activity, which was possibly also a limiting factor in the use, the psychotomometic side effects of potentiating morphine, oxycodone, and other opioids with scopolamine (respectively in the Twilight Sleep technique and the combination drug Skophedal, which was eukodal (oxycodone), scopolamine and ephedrine, called the “wonder drug of the 1930s” after its invention in Germany in 1928, but only rarely specially compounded today) (q.q.v.).

Sensory Deprivation Hallucination

Hallucinations can be caused by sensory deprivation when it occurs for prolonged periods of time, and almost always occurs in the modality being deprived (visual for blindfolded/darkness, auditory for muffled conditions, etc).

Experimentally-Induced Hallucinations

Anomalous experiences, such as so-called benign hallucinations, may occur in a person in a state of good mental and physical health, even in the apparent absence of a transient trigger factor such as fatigue, intoxication or sensory deprivation.

The evidence for this statement has been accumulating for more than a century. Studies of benign hallucinatory experiences go back to 1886 and the early work of the Society for Psychical Research, which suggested approximately 10% of the population had experienced at least one hallucinatory episode in the course of their life. More recent studies have validated these findings; the precise incidence found varies with the nature of the episode and the criteria of “hallucination” adopted, but the basic finding is now well-supported.

Non-Celiac Gluten Sensitivity

There is tentative evidence of a relationship with non-celiac gluten sensitivity, the so-called “gluten psychosis”.

Pathophysiology

Dopaminergic and Serotoninergic Hallucinations

It has been reported that in serotoninergic hallucinations, the person maintains an awareness that they is hallucinating, unlike dopaminergic hallucinations.

Neuroanatomy

Hallucinations are associated with structural and functional abnormalities in primary and secondary sensory cortices. Reduced grey matter in regions of the superior temporal gyrus/middle temporal gyrus, including Broca’s area, is associated with auditory hallucinations as a trait, while acute hallucinations are associated with increased activity in the same regions along with the hippocampus, parahippocampus, and the right hemispheric homologue of Broca’s area in the inferior frontal gyrus. Grey and white matter abnormalities in visual regions are associated with visual hallucinations in diseases such as Alzheimer’s disease, further supporting the notion of dysfunction in sensory regions underlying hallucinations.

One proposed model of hallucinations posits that over-activity in sensory regions, which is normally attributed to internal sources via feedforward networks to the inferior frontal gyrus, is interpreted as originating externally due to abnormal connectivity or functionality of the feedforward network. This is supported by cognitive studies those with hallucinations, who have demonstrated abnormal attribution of self generated stimuli.

Disruptions in thalamocortical circuitry may underlie the observed top down and bottom up dysfunction. Thalamocortical circuits, composed of projections between thalamic and cortical neurons and adjacent interneurons, underlie certain electrophysical characteristics (gamma oscillations) that are underlie sensory processing. Cortical inputs to thalamic neurons enable attentional modulation of sensory neurons. Dysfunction in sensory afferents, and abnormal cortical input may result in pre-existing expectations modulating sensory experience, potentially resulting in the generation of hallucinations. Hallucinations are associated with less accurate sensory processing, and more intense stimuli with less interference are necessary for accurate processing and the appearance of gamma oscillations (called “gamma synchrony”). Hallucinations are also associated with the absence of reduction in P50 amplitude in response to the presentation of a second stimuli after an initial stimulus; this is thought to represent failure to gate sensory stimuli, and can be exacerbated by dopamine release agents.

Abnormal assignment of salience to stimuli may be one mechanism of hallucinations. Dysfunctional dopamine signalling may lead to abnormal top down regulation of sensory processing, allowing expectations to distort sensory input.

Treatments

There are few treatments for many types of hallucinations. However, for those hallucinations caused by mental disease, a psychologist or psychiatrist should be consulted, and treatment will be based on the observations of those doctors. Antipsychotic and atypical antipsychotic medication may also be utilised to treat the illness if the symptoms are severe and cause significant distress. For other causes of hallucinations there is no factual evidence to support any one treatment is scientifically tested and proven. However, abstaining from hallucinogenic drugs, stimulant drugs, managing stress levels, living healthily, and getting plenty of sleep can help reduce the prevalence of hallucinations. In all cases of hallucinations, medical attention should be sought out and informed of one’s specific symptoms.

Epidemiology

Several recent studies on the prevalence of hallucinations in the general population have appeared. A 2020 US study indicated a lifetime prevalence of 10-15% for vivid sensory hallucinations. Compared with the English Sidgewick Study of 1894, relative frequencies of sensory modalities differed in the US with fewer visual hallucinations.

Book: Best Practices and Barriers to Engaging People with Substance Use Disorders in Treatment

Book Title:

Best Practices and Barriers to Engaging People with Substance Use Disorders in Treatment.

Author(s): Peggy O’Brien, Erika Crable, Catherine Fullerton, and Lauren Hughey.

Year: March 2019.

Edition: First (1st).

Publisher: US Department of Health and Human Services.

Type(s): eBook.

Synopsis:

In 2015, 20.8 million people aged 12 years or older (7.8% of the United States population) had a substance use disorder (SUD) in the previous year. Approximately 75% of this group, or 15.7 million Americans, had an alcohol use disorder,
2.0 million had a prescription opioid use disorder (OUD), and about 0.6 million had a heroin use disorder.

Since 1999, opioid-related overdose deaths in the United States have quadrupled, with more than 15,000 individuals experiencing prescription drug-related overdose deaths in 2015. Even though evidence-based SUD treatments are effective, rates of treatment receipt are quite low. In 2015, only 18% of the population with SUDs, or 3.7 million people, received SUD treatment – a number that has not increased significantly since 2002.

Only about 48% of patients who enter SUD treatment actually complete it.

You can access the book, for free, here.

Book: Approaches to Drug Abuse Counselling

Book Title:

Approaches to Drug Abuse Counselling.

Author(s): National Institute on Drug Abuse (NIDA).

Year: 2000.

Edition: First (1st).

Publisher: US Government Printing Office.

Type(s): eBook.

Synopsis:

Dual disorders recovery counselling (DDRC) is an integrated approach to treatment of patients with drug use disorders and comorbid psychiatric disorders.

The DDRC model, which integrates individual and group addiction counselling approaches with psychiatric interventions, attempts to balance the focus of treatment so that both the patient’s addiction and psychiatric issues are addressed.

The DDRC model is based on the assumption that there are several treatment phases that patients may go through.

You can access the book, for free, here.

Book: Integrating Behavioural Therapies with Medications in the Treatment of Drug Dependence

Book Title:

Integrating Behavioural Therapies With Medications in the Treatment of Drug Dependence (National Institute on Drug Abuse Research Monograph Series).

Author(s): Lisa Simon Onken (PhD), Jack D. Blaine (MD), and John J. Boren (PhD.

Year: 1995.

Edition: First (1st).

Publisher: US Government Printing Office.

Type(s): eBook.

Synopsis:

It is no revelation that drug dependence is a complex problem with behavioural, cognitive, psychosocial, and biological dimensions and may be treated with behavioural therapy (including behaviour therapy, psychotherapy, and counselling), and, where available, pharmacotherapy.

Drug use can be reduced behaviourally with appropriate manipulation of reinforcements within the environment (Higgins et al. 1993). Continued improvements over time in drug use can be initiated by cognitive behavioural psychotherapies to modify cognitions that perpetuate drug use (Carroll et al., submitted for publication), and a reduced likelihood of
relapse has been engendered by specialised training approaches (Rohsenow et al., in press).

Methadone, of course, has long been recognised as an effective pharmacotherapy to reduce opiate use, and its biological mechanism of action is well understood.

You can access the book, for free, here.

Book: Psychotherapy And Counselling In The Treatment Of Drug Abuse

Book Title:

Psychotherapy And Counselling In The Treatment Of Drug Abuse (National Institute on Drug Abuse Research Monograph Series).

Author(s): Lisa Simon Onken (PhD) and Jack D. Blaine (MD).

Year: 1990.

Edition: First (1st).

Publisher: US Government Printing Office.

Type(s): eBook.

Synopsis:

Drug abuse treatment occurs in a multitude of forms. It may be provided in outpatient or inpatient settings, be publicly or privately funded, and mayor may not involve the administration of medication. The differences among the philosophies of, and the services provided in, various drug abuse treatment programmes may be enormous. What is remarkable is that some form of drug abuse counselling or psychotherapy is almost invariably a part of every type of comprehensive drug abuse treatment. Individual therapy or counselling is available in about 99% of the drug-free, methadone-maintenance, and multiple-modality drug abuse treatment units in this country (National Drug and Alcoholism Treatment Unit Survey 1982). It is also available in approximately 97% of the detoxification units.

You can access the book, for free, here.

Book: Encyclopedia of Psychedelics

Book Title:

Encyclopedia of Psychedelics.

Author(s): Peter Stafford.

Year: 1993.

Edition: Third (3rd), Expanded Edition.

Publisher: Ronin Publishing.

Type(s): Paperback and Kindle.

Synopsis:

Traces the history of the use of hallucinogenic drugs and discusses the psychological and physical effects of LSD, marijuana, mescaline, and other drugs.